Remote Preconditioning Reduces Microcirculatory Disorders in Pancreatic Ischemia/Reperfusion Injury

Abstract

Remote preconditioning (RPC) can protect from ischemia/reperfusion injury (IRI). We investigated the influence of RPC in pancreatic IRI. Wistar rats were randomized to 2 hours of ischemia and 2 hours of reperfusion of a pancreatic tail segment with or without 15 minutes of infrarenal ischemia 60 minutes before IRI. Microcirculatory measurements before ischemia and 1 and 2 hours after reperfusion included functional capillary density and leukocyte adherence in postcapillary venules, quantified by intravital fluorescence microscopy. Histology and tissue myeloperoxidase activity were further parameters of pancreatic injury. Remote preconditioning caused an improvement of microcirculation (functional capillary density: 1 hour after reperfusion, 460 +/- 13 vs 350 +/- 9 cm/cm2; 2 hours after reperfusion, 437 +/- 13 vs 295 +/- 13 cm/cm2; P < 0.01) and reduced inflammatory tissue response (leukocyte adherence in postcapillary venules: 2 hours after reperfusion, 155 +/- 55 vs 748 +/- 187 cells/mm2; P < 0.01). Histology was significantly better in preconditioned animals (IR, 8.1+/- 1.3 score points; RPC, 6.2 +/- 1.3 score points; P < 0.05). The difference in myeloperoxidase activity was not significant (ischemia/reperfusion [IR], 105 +/- 72; RPC, 245 +/- 209 mU x min(-1) x mg(ti)(-1); P = 0.13). With our dynamic functional microcirculatory measurements, we could demonstrate that RPC is a feasible method to reduce experimental pancreatic IRI. This was seen in an attenuation of nutritive tissue perfusion and a reduction of inflammatory tissue response and a lower histological damage. Because it is easy to perform before organ harvest, RPC could be a step to improve organ procurement in pancreas transplantation. Clinical studies are the next step to evaluate RPC in pancreas transplantation.